Social class differences in mortality, morbidity and health functioning persist in the USA, UK and other industrialized countries. Indeed for mortality they may be widening. Such socioeconomic (SES) gradients in health are present throughout the lifespan persisting into the eighth decade. Changes of health with age are heterogeneous with important environmental determinants, which include SES. We will establish patterns and determinants of change of health in relation to age and SES. Further, we will examine whether the causes and consequences of within-person changes of health with age are different from those found cross-sectionally. In the British civil service there is an inverse social gradient in morbidity and mortality. The broad long term objective of the Whitehall II study is to explain these socioeconomic differences in health. The WhitehallII study of 10 308 male and female civil servants, aged 35-55 years at sntry (1985-1988), was established to examine role of specific psychosocial, lifestyle, biochemical and physiological factors as possible explanations of these inequalities. True age related changes in these exposures, or cumulative exposure measured longitudinally, are hypothesized to predict changes in SES differences in health with age. At the 10 year follow up of the cohort, NIA support funded collection of data to repeat outcome measures of health functioning, costive functioning, components of the metabolic syndrome and ApoE genotyping. The aims of the proposal are: 1. To describe and explain patterns of change with age in health status in relation to SES. 2. To determine if the gradient in health functioning differs from pre-retirement to retirement. 3. To examinethe relationship between SES and change in cognitive function with age. 4. to investigate specific biological pathways linking SES by examining the causes and consequences of their change with age. The Whitehall II study is uniquely po:ised to address these questions, offering: civil service employment grade as an excellent measure of SES; longitudinal design with participants comparatively young at entry allowingthe detection of antecedents of change; repeated measures of exposures; a wide range of exposure data; substantial power to detect age-related change, and its interaction with SES; wide range of health outcomes includinghealth and cognitive functioning, components of the metabolic syndrome, mortality, non-fatal diagnoses and sickness absence. We now request funding to analyze the data collected to date and to contribute to specific elements of the 15year follow-up of the cohort. With NIA support for Phase 7, we will be able to build on Whitehall II. It will enable us to accumulate more endpoints and track health functioning into older age, relate them to early life and mid-life exposures, and thereby allow us to establish psychosocial and biological pathways of disease and health inequalities. PERFORMANCE S\TG(S)(organization, city, state) International Centre for Health & Society DepC of Epidemiology & Public Health University College London 1-1!) Torrington Place London WC1E 6BT KEY PERSONNEL.SeeInstructionson Page 11.Usecontinuationpagesasneededto providetherequiredinformation inthe format shown below. Name Organization Role onProject Professor Michael Marmot UCL (in alphabetical order) Dr Eric Branner UCL Professor Vein Farewell UCL Dr Rebecca Fuhrer UCL Dr Jenny Head UCL Dr Harry Hemingway UCL Dr Paul Higgs UCL Professor Steven Humphries UCL Principal Investigator/ Director Co-Investigator / Senior Lecturer Consultant/Statistician Co-Investigator/Senior Res Scientist Co-Investigator/ Statistician/ SnLecturer Co-Investigator/ Senior Lecturer Collaborator/Lecturer Co-Investigator/Collaborator PHS 35)8 (Rev.5/95) Page 2 BB Number pages consecutively at the bottom throughout the application. Donoj use suffixes such as 3a, 3b. PrincipalInvestigator/ProgramDirector (Last,ffrsl.middle): Marmot, Michael Gideon Dr Meena Kumari UCL Co-Investigator /Research Fellow Dr Pekka Martikainen UCL ResearchFellow Ms Gill Mein UCL Doctoral Fellow Dr Martin Shipley UCL Senior Lect/Statistician Dr Stephen Stansfeld UCL Co-Investigator/Co-Director/Reader 1 O Q 0) O CC i [unreadable][unreadable] u O O F'HS39B(Rev.5/9S) Page_L Mumber pagesconsecutively al thebottomthroughout the application.Dono/use suffixes suchas3a,3b. CC PrincipalInvestigator/Program Director(Last, first, middle): Marmot, Michael Gideon Typethe name ofthe principalinvestigator/programdirector atthe topofeachprintedpageandeach continuation page.(Fortypespecifications,see instructions onpage 6.) RESEARCHGRANT TABLE OF CONTENTS PageNumbers FacePage 1 description,